Rimegepant for Irritable Bowel Syndrome

Overseen By Deborah Eckert, RN

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Mayo Clinic

Must not be taking: CYP3A4 inhibitors, CYP3A4 inducers

Disqualifiers: Depression, Substance abuse, Pregnancy, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 4 weeks

24 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you've had a significant change in antidepressant or pain medications in the last four weeks. Also, you cannot use strong CYP3A4 inhibitors or inducers.

Is Rimegepant generally safe for humans?

Rimegepant, used for treating migraines, is generally well tolerated in humans, with no serious liver or heart-related side effects reported in clinical trials. Most side effects were mild or moderate and did not lead to stopping the treatment. ^{1 2 3 4 5}

How is the drug Rimegepant unique for treating irritable bowel syndrome?

Rimegepant is unique for treating irritable bowel syndrome because it is primarily known for its use in treating migraines, and its application for IBS is novel. Unlike traditional IBS treatments that target serotonin receptors or opioid receptors, Rimegepant's mechanism of action involves blocking a protein called CGRP (calcitonin gene-related peptide), which is not a common target in IBS therapies. ^{6 7 8 9 10}

What is the purpose of this trial?

The primary aim of this study is to evaluate the efficacy of rimegepant on abdominal pain scores in participants with non-constipation IBS.

Research Team

Michael Camilleri, M.D., D.Sc.

Principal Investigator

Mayo Clinic

Eligibility Criteria

Adults aged 18-65 with non-constipation IBS and chronic abdominal pain can join this trial. They must have a documented diagnosis, experience significant pain, and be able to consent. Excluded are those with severe depression, substance abuse issues, certain medical conditions like liver or kidney disease, recent changes in pain medication, or women who could be pregnant.

Inclusion Criteria

I am able to understand and agree to the study's procedures and risks.

My pain level is more than 3 on a scale.

I have IBS without constipation and chronic abdominal pain for over 3 months.

Exclusion Criteria

I am not pregnant and will use effective birth control during the trial.

I experience nausea several times a week or daily.

Alcohol or illicit substance dependence or abuse in the past 12 months

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2 weeks

1 visit (in-person)

Run-in

Participants undergo a 2-week run-in period to establish baseline measurements

2 weeks

Daily diary entries

Treatment

Participants receive either rimegepant or placebo every other day for 4 weeks

4 weeks

Daily diary entries, 1 visit (in-person) for assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person)

Treatment Details

Interventions

• Rimegepant

Trial Overview The study is testing if Rimegepant (a drug currently used for migraines) can reduce stomach pain in people with Irritable Bowel Syndrome that doesn't involve constipation. Participants will either receive Rimegepant or a placebo to compare the effectiveness.

Participant Groups

Group I: rimegepant Experimental Treatment 1 Intervention

* Rimegepant 75mg oral dissolving tablet (ODT) * Formulation and Dosing as FDA-approved for Migraine Prevention: 75 mg Every Other Day (EOD) for 4 weeks/30 days

Group II: placebo Placebo Group 1 Intervention

Placebo ODT appearing identical to the experimental formulation and administered every other day for 4 weeks/30 days

Rimegepant is already approved in United States, European Union, Canada, United Kingdom for the following indications:

Approved in United States as Nurtec ODT for:

• Acute treatment of migraine with or without aura in adults
• Preventative treatment of episodic migraine in adults

Approved in European Union as Vydura for:

• Prophylaxis and acute treatment of migraine in adults

Approved in Canada as Nurtec ODT for:

• Acute treatment of migraine with or without aura in adults
• Preventative treatment of episodic migraine in adults

Approved in United Kingdom as Vydura for:

• Prophylaxis and acute treatment of migraine in adults

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

Pfizer

Industry Sponsor

Trials

4,712

Recruited

50,980,000+

Known For

Vaccine Innovations

Top Products

Viagra, Zoloft, Lipitor, Prevnar 13

Albert Bourla

Pfizer

Chief Executive Officer since 2019

PhD in Biotechnology of Reproduction, Aristotle University of Thessaloniki

Patrizia Cavazzoni

Pfizer

Chief Medical Officer

MD from McGill University

Findings from Research

Rimegepant is an effective treatment for migraines, showing significant pain relief and reduction in bothersome symptoms compared to placebo in phase III trials, and it can also reduce the number of monthly migraine days when used preventively.

The medication is generally well tolerated, with no signs of liver or heart-related side effects, making it a safe option for adults managing migraines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rimegepant: A Review in the Acute Treatment and Preventive Treatment of Migraine. Blair, HA.[2023]

Rimegepant, an oral CGRP receptor antagonist, has shown significant efficacy in treating migraines, providing pain relief and symptom improvement for up to 48 hours after a single dose, based on completed phase II and III trials.

The medication was well tolerated with only mild to moderate adverse events reported, leading to its FDA approval for acute migraine treatment on February 27, 2020.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rimegepant for the treatment of migraine. Negro, A., Martelletti, P.[2021]

Rimegepant (NURTEC ODT®) is an orally disintegrating tablet that acts as a highly-selective antagonist of calcitonin gene-related peptide, specifically designed for the acute treatment of migraines.

In February 2020, rimegepant ODT received its first global approval in the USA for treating migraines with or without aura in adults, marking a significant milestone in its development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rimegepant: First Approval. Scott, LJ.[2022]

Rimegepant significantly improves outcomes for migraine patients, including freedom from pain and pain relief at 2 hours, with odds ratios indicating strong efficacy compared to placebo.

The treatment shows sustained benefits at 24 hours and does not appear to increase the risk of adverse events, suggesting it is a safe option for migraine management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Rimegepant for Migraine Patients: A Meta-analysis of Randomized Controlled Studies. Yang, C., Zhang, Y.[2023]

Rimegepant, taken every other day, significantly reduced the mean number of migraine days per month compared to placebo, with a difference of -0.8 days, indicating its efficacy as a preventive treatment for migraines.

The safety profile of rimegepant was comparable to that of placebo, with similar rates of adverse events and no serious safety concerns reported during the study involving 747 participants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral rimegepant for preventive treatment of migraine: a phase 2/3, randomised, double-blind, placebo-controlled trial. Croop, R., Lipton, RB., Kudrow, D., et al.[2021]

Ramosetron significantly improves overall symptoms of irritable bowel syndrome with diarrhea (IBS-D), including abdominal discomfort and stool consistency, based on a meta-analysis of four trials with 1623 participants.

While ramosetron is effective, it may lead to increased instances of hard stool and constipation, but no serious adverse events were reported, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ramosetron for the treatment of irritable bowel syndrome with diarrhea: a systematic review and meta-analysis of randomized controlled trials. Qi, Q., Zhang, Y., Chen, F., et al.[2018]

In a study of 418 patients with diarrhea-predominant irritable bowel syndrome (IBS-D), ramosetron, a 5-HT3-receptor antagonist, significantly improved IBS symptoms compared to placebo, with a 47% positive response rate in the treatment group versus 27% in the placebo group.

Ramosetron was well-tolerated with only 7% of patients reporting adverse events, and no serious side effects like severe constipation or ischemic colitis were observed during long-term treatment, indicating its potential safety for extended use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term efficacy and safety of ramosetron in the treatment of diarrhea-predominant irritable bowel syndrome. Chiba, T., Yamamoto, K., Sato, S., et al.[2021]

Eluxadoline is a newly approved medication for treating irritable bowel syndrome with diarrhea (IBS-D), showing efficacy in reducing bowel habit changes and abdominal pain in both short and long-term use.

While eluxadoline offers a new treatment option for IBS-D, its use may be limited by a small risk of side effects such as sphincter of Oddi spasm and mild pancreatitis, which need to be considered in treatment plans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New therapeutic options for IBS: the role of the first in class mixed µ- opioid receptor agonist and δ-opioid receptor antagonist (mudelta) eluxadoline. Corsetti, M., Whorwell, P.[2018]

Ramosetron, a selective 5-HT3 receptor antagonist, has shown significant efficacy in treating irritable bowel syndrome with diarrhea (IBS-D) in two randomized controlled studies involving 957 patients, improving symptom relief compared to placebo.

Ramosetron has a better safety profile than other 5-HT3 receptor antagonists, with a lower incidence of constipation and no reported cases of ischemic colitis, making it a promising treatment option for IBS-D.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The clinical potential of ramosetron in the treatment of irritable bowel syndrome with diarrhea (IBS-D). Min, YW., Rhee, PL.[2020]

In a rat model of irritable bowel syndrome (IBS), increased levels of 5-hydroxytryptamine (5-HT) and spinal NR2B receptors were linked to visceral hypersensitivity, suggesting their significant role in IBS symptoms.

Treatment with Ro25-6981 (a NR2B antagonist) and amitriptyline (a 5-HT antagonist) reduced the expression of these receptors and inflammatory markers, indicating potential therapeutic effects for managing IBS-related hypersensitivity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Activation of 5-HT and NR2B contributes to visceral hypersensitivity in irritable bowel syndrome in rats. Chen, MX., Chen, Y., Fu, R., et al.[2022]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Rimegepant: A Review in the Acute Treatment and Preventive Treatment of Migraine. [2023]

2. Spain pubmed.ncbi.nlm.nih.gov

Rimegepant for the treatment of migraine. [2021]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Rimegepant: First Approval. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Rimegepant for Migraine Patients: A Meta-analysis of Randomized Controlled Studies. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Oral rimegepant for preventive treatment of migraine: a phase 2/3, randomised, double-blind, placebo-controlled trial. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Ramosetron for the treatment of irritable bowel syndrome with diarrhea: a systematic review and meta-analysis of randomized controlled trials. [2018]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Long-term efficacy and safety of ramosetron in the treatment of diarrhea-predominant irritable bowel syndrome. [2021]

8. England pubmed.ncbi.nlm.nih.gov

New therapeutic options for IBS: the role of the first in class mixed µ- opioid receptor agonist and δ-opioid receptor antagonist (mudelta) eluxadoline. [2018]

9. England pubmed.ncbi.nlm.nih.gov

The clinical potential of ramosetron in the treatment of irritable bowel syndrome with diarrhea (IBS-D). [2020]

10. United States pubmed.ncbi.nlm.nih.gov

Activation of 5-HT and NR2B contributes to visceral hypersensitivity in irritable bowel syndrome in rats. [2022]